BLAR_STAAU
ID BLAR_STAAU Reviewed; 585 AA.
AC P18357;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1990, sequence version 1.
DT 25-MAY-2022, entry version 100.
DE RecName: Full=Regulatory protein BlaR1;
GN Name=blaR1;
OS Staphylococcus aureus.
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=1280;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=NCTC 9789 / PS80; TRANSPOSON=Tn552;
RX PubMed=2170815; DOI=10.1111/j.1365-2958.1990.tb00669.x;
RA Rowland S.J., Dyke K.G.H.;
RT "Tn552, a novel transposable element from Staphylococcus aureus.";
RL Mol. Microbiol. 4:961-975(1990).
RN [2]
RP FUNCTION, AND MUTAGENESIS OF HIS-201 AND GLU-202.
RX PubMed=11239156; DOI=10.1126/science.1055144;
RA Zhang H.Z., Hackbarth C.J., Chansky K.M., Chambers H.F.;
RT "A proteolytic transmembrane signaling pathway and resistance to beta-
RT lactams in staphylococci.";
RL Science 291:1962-1965(2001).
RN [3]
RP FUNCTION, MUTAGENESIS OF SER-389 AND LYS-392, AND CARBOXYLATION AT LYS-392.
RX PubMed=12591921; DOI=10.1074/jbc.m300611200;
RA Golemi-Kotra D., Cha J.Y., Meroueh S.O., Vakulenko S.B., Mobashery S.;
RT "Resistance to beta-lactam antibiotics and its mediation by the sensor
RT domain of the transmembrane BlaR signaling pathway in Staphylococcus
RT aureus.";
RL J. Biol. Chem. 278:18419-18425(2003).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 331-585, DOMAIN, ACTIVE SITE, AND
RP FUNCTION.
RX PubMed=15506754; DOI=10.1021/ja044742u;
RA Birck C., Cha J.Y., Cross J., Schulze-Briese C., Meroueh S.O.,
RA Schlegel H.B., Mobashery S., Samama J.P.;
RT "X-ray crystal structure of the acylated beta-lactam sensor domain of BlaR1
RT from Staphylococcus aureus and the mechanism of receptor activation for
RT signal transduction.";
RL J. Am. Chem. Soc. 126:13945-13947(2004).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 331-585, AND DOMAIN.
RX PubMed=15322076; DOI=10.1074/jbc.m407054200;
RA Wilke M.S., Hills T.L., Zhang H.Z., Chambers H.F., Strynadka N.C.;
RT "Crystal structures of the Apo and penicillin-acylated forms of the BlaR1
RT beta-lactam sensor of Staphylococcus aureus.";
RL J. Biol. Chem. 279:47278-47287(2004).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 332-583, CARBOXYLATION AT
RP LYS-392, ACTIVE SITE, AND DOMAIN.
RX PubMed=21775440; DOI=10.1074/jbc.m111.252189;
RA Borbulevych O., Kumarasiri M., Wilson B., Llarrull L.I., Lee M., Hesek D.,
RA Shi Q., Peng J., Baker B.M., Mobashery S.;
RT "Lysine Nzeta-decarboxylation switch and activation of the beta-lactam
RT sensor domain of BlaR1 protein of methicillin-resistant Staphylococcus
RT aureus.";
RL J. Biol. Chem. 286:31466-31472(2011).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 332-583, DOMAIN, AND MUTAGENESIS
RP OF ASN-439.
RX PubMed=22262858; DOI=10.1074/jbc.m111.333179;
RA Kumarasiri M., Llarrull L.I., Borbulevych O., Fishovitz J., Lastochkin E.,
RA Baker B.M., Mobashery S.;
RT "An amino acid position at crossroads of evolution of protein function:
RT antibiotic sensor domain of BlaR1 protein from Staphylococcus aureus versus
RT clasS D beta-lactamases.";
RL J. Biol. Chem. 287:8232-8241(2012).
CC -!- FUNCTION: Integral membrane protein involved in sensing of the presence
CC of beta-lactam antibiotics and transduction of the information to the
CC cytoplasm. Mechanistically, activation of the signal transducer
CC involves acylation of a serine in the C-terminal sensor domain upon
CC binding of the beta-lactam antibiotic (PubMed:12591921,
CC PubMed:15506754). In turn, a conformational change occurs and the
CC signal is transmitted from the cell surface to the cytoplasm. There,
CC the zinc protease domain is activated and initiates autoproteolysis as
CC well as cleavage of the transcriptional repressor BlaI leading to
CC derepression of antibiotic resistance genes (PubMed:11239156).
CC {ECO:0000269|PubMed:11239156, ECO:0000269|PubMed:12591921,
CC ECO:0000269|PubMed:15506754}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P12287};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:P12287}.
CC -!- PTM: Carboxylation occurs on two lysine residues. Carboxylation at
CC 'Lys-392' activates the active site serine residue for acylation
CC (PubMed:12591921). On acylation, the lysine side chain experiences a
CC spontaneous decarboxylation that entraps the sensor in its activated
CC state (PubMed:15506754, PubMed:21775440). {ECO:0000269|PubMed:12591921,
CC ECO:0000269|PubMed:15506754, ECO:0000269|PubMed:21775440}.
CC -!- SIMILARITY: Belongs to the peptidase M56 family. {ECO:0000305}.
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DR EMBL; X52734; CAA36952.1; -; Genomic_DNA.
DR PDB; 1XA1; X-ray; 1.80 A; A/B/C/D=331-585.
DR PDB; 1XA7; X-ray; 2.40 A; A/B=331-585.
DR PDB; 1XKZ; X-ray; 1.75 A; A/B/C/D=331-585.
DR PDB; 3Q81; X-ray; 2.00 A; A/B=332-583.
DR PDB; 3Q82; X-ray; 2.10 A; A/B=332-583.
DR PDB; 3UY6; X-ray; 2.10 A; A/B=332-583.
DR PDB; 6O9W; X-ray; 1.95 A; A/B=330-585.
DR PDBsum; 1XA1; -.
DR PDBsum; 1XA7; -.
DR PDBsum; 1XKZ; -.
DR PDBsum; 3Q81; -.
DR PDBsum; 3Q82; -.
DR PDBsum; 3UY6; -.
DR PDBsum; 6O9W; -.
DR AlphaFoldDB; P18357; -.
DR SMR; P18357; -.
DR DrugBank; DB03530; Acylated ceftazidime.
DR DrugBank; DB02968; Penicillin G Acyl-Serine.
DR MEROPS; M56.001; -.
DR PRIDE; P18357; -.
DR EvolutionaryTrace; P18357; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0008658; F:penicillin binding; IEA:InterPro.
DR Gene3D; 3.40.710.10; -; 1.
DR InterPro; IPR012338; Beta-lactam/transpept-like.
DR InterPro; IPR001460; PCN-bd_Tpept.
DR InterPro; IPR008756; Peptidase_M56.
DR Pfam; PF05569; Peptidase_M56; 1.
DR Pfam; PF00905; Transpeptidase; 1.
DR SUPFAM; SSF56601; SSF56601; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Membrane; Transmembrane; Transmembrane helix;
KW Transposable element.
FT CHAIN 1..585
FT /note="Regulatory protein BlaR1"
FT /id="PRO_0000195470"
FT TOPO_DOM 1..4
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P12287"
FT TRANSMEM 5..22
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P12287"
FT TOPO_DOM 23..31
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P12287"
FT TRANSMEM 32..48
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P12287"
FT TOPO_DOM 49..104
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P12287"
FT TRANSMEM 105..122
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P12287"
FT TOPO_DOM 123..311
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P12287"
FT TRANSMEM 312..328
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P12287"
FT TOPO_DOM 329..585
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P12287"
FT REGION 331..585
FT /note="Beta-lactam antibiotic sensor domain"
FT /evidence="ECO:0000269|PubMed:15322076,
FT ECO:0000269|PubMed:15506754, ECO:0000269|PubMed:21775440,
FT ECO:0000269|PubMed:22262858"
FT ACT_SITE 389
FT /note="Acyl-ester intermediate"
FT /evidence="ECO:0000269|PubMed:15506754,
FT ECO:0000269|PubMed:21775440"
FT MOD_RES 392
FT /note="N6-carboxylysine"
FT /evidence="ECO:0000269|PubMed:12591921"
FT MUTAGEN 201
FT /note="H->A: Complete loss of transcriptional repressor
FT BlaI cleavage."
FT /evidence="ECO:0000269|PubMed:11239156"
FT MUTAGEN 202
FT /note="E->A: Complete loss of transcriptional repressor
FT BlaI cleavage."
FT /evidence="ECO:0000269|PubMed:11239156"
FT MUTAGEN 389
FT /note="S->A: Complete loss of the acylation step."
FT /evidence="ECO:0000269|PubMed:12591921"
FT MUTAGEN 392
FT /note="K->A: Almost complete loss of the acylation step."
FT /evidence="ECO:0000269|PubMed:12591921"
FT MUTAGEN 439
FT /note="N->V: Exhibits enhanced beta-lactamase activity with
FT cephalosporins as substrates but not with penicillins and
FT carbapenems."
FT /evidence="ECO:0000269|PubMed:22262858"
FT TURN 334..337
FT /evidence="ECO:0007829|PDB:3Q81"
FT STRAND 345..350
FT /evidence="ECO:0007829|PDB:1XKZ"
FT HELIX 353..356
FT /evidence="ECO:0007829|PDB:1XKZ"
FT STRAND 360..367
FT /evidence="ECO:0007829|PDB:1XKZ"
FT TURN 368..371
FT /evidence="ECO:0007829|PDB:1XKZ"
FT STRAND 372..377
FT /evidence="ECO:0007829|PDB:1XKZ"
FT HELIX 378..381
FT /evidence="ECO:0007829|PDB:1XKZ"
FT STRAND 383..385
FT /evidence="ECO:0007829|PDB:1XKZ"
FT HELIX 388..391
FT /evidence="ECO:0007829|PDB:1XKZ"
FT HELIX 392..401
FT /evidence="ECO:0007829|PDB:1XKZ"
FT STRAND 402..405
FT /evidence="ECO:0007829|PDB:1XA7"
FT HELIX 422..424
FT /evidence="ECO:0007829|PDB:1XKZ"
FT HELIX 430..435
FT /evidence="ECO:0007829|PDB:1XKZ"
FT HELIX 439..446
FT /evidence="ECO:0007829|PDB:1XKZ"
FT HELIX 451..461
FT /evidence="ECO:0007829|PDB:1XKZ"
FT STRAND 471..473
FT /evidence="ECO:0007829|PDB:1XKZ"
FT TURN 474..477
FT /evidence="ECO:0007829|PDB:1XKZ"
FT HELIX 484..496
FT /evidence="ECO:0007829|PDB:1XKZ"
FT HELIX 503..513
FT /evidence="ECO:0007829|PDB:1XKZ"
FT STRAND 514..517
FT /evidence="ECO:0007829|PDB:1XKZ"
FT STRAND 519..532
FT /evidence="ECO:0007829|PDB:1XKZ"
FT STRAND 535..549
FT /evidence="ECO:0007829|PDB:1XKZ"
FT STRAND 551..562
FT /evidence="ECO:0007829|PDB:1XKZ"
FT HELIX 565..578
FT /evidence="ECO:0007829|PDB:1XKZ"
FT TURN 579..582
FT /evidence="ECO:0007829|PDB:1XA1"
SQ SEQUENCE 585 AA; 69246 MW; 597CAD94E9CF21CE CRC64;
MAKLLIMSIV SFCFIFLLLL FFRYILKRYF NYMLNYKVWY LTLLAGLIPF IPIKFSLFKF
NNVNNQAPTV ESKSHDLNHN INTTKPIQEF ATDIHKFNWD SIDNISTVIW IVLVIILSFK
FLKALLYLKY LKKQSLYLNE NEKNKIDTIL FNHQYKKNIV IRKAETIQSP ITFWYGKYII
LIPSSYFKSV IDKRLKYIIL HEYAHAKNRD TLHLIIFNIF SIIMSYNPLV HIVKRKIIHD
NEVEADRFVL NNINKNEFKT YAESIMDSVL NVPFFNKNIL SHSFNGKKSL LKRRLINIKE
ANLKKQSKLI LIFICIFTFL LMVIQSQFLM GQSITDYNYK KPLHNDYQIL DKSKIFGSNS
GSFVMYSMKK DKYYIYNEKE SRKRYSPNST YKIYLAMFGL DRHIINDENS RMSWNHKHYP
FDAWNKEQDL NTAMQNSVNW YFERISDQIP KNYTATQLKQ LNYGNKNLGS YKSYWMEDSL
KISNLEQVIV FKNMMEQNNH FSKKAKNQLS SSLLIKKNEK YELYGKTGTG IVNGKYNNGW
FVGYVITNHD KYYFATHLSD GKPSGKNAEL ISEKILKEMG VLNGQ
